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GABA consumption during early pregnancy impairs endometrial receptivity and embryo development in mice
Author(s) -
Tian Na,
Liang Hao,
Luo Wenping,
Wang Xiaojie,
Cao Ke,
Zhang Qian,
Tan Yi,
Tan Dongmei
Publication year - 2020
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.22473
Subject(s) - embryo , pregnancy , gamma aminobutyric acid , uterus , endometrium , endocrinology , gabaa receptor , receptor , medicine , receptivity , biology , andrology , microbiology and biotechnology , genetics
γ‐Aminobutyrate (GABA) is commonly used as a food supplement and a health care product by young females, due to its positive roles in relieving stress, alleviating anxiety, and improving sleep. However, its recommended daily dose in different products varies widely. Besides, it is unknown whether, and how, GABA consumption during early pregnancy influences pregnancy establishment. In this study, we found that when pregnant mice were treated with a high (12.5 mg/g) dose of GABA (orally) during preimplantation, there was a reduction in the number of implantation sites on day 5 of pregnancy. Also, among these unimplanted embryos, most exhibited morphological degeneration and developmental retardation, and only a few of them developed into blastocysts but could not implant into the uterus. Moreover, the expression of uterine receptivity–related factors—LIF, E‐cadherin, and HOXA10—were all downregulated, while the number of uterine glands was reduced in the high GABA dose group. Finally, in vitro results demonstrated that GABA (ranging from 10 to 50 μg/μL) markedly inhibited preimplantation embryo development in a dose‐response manner. However, this inhibitory effect was not observed when the embryos were pretreated with 40 μΜ 2‐hydroxysaclofen, a GABA B antagonist, indicating that GABA exerts its inhibitory effects via its B‐type receptor. Our results suggest that exposure to certain GABA concentrations, during early pregnancy, can impair preimplantation embryo development via its B‐type receptor, and endometrial receptivity, which greatly disturbs early embryo implantation in mice. These findings could raise concerns about GABA consumption during the early stages of pregnancy.